rs2229532

Positions:

chr19-11576317-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001611.5(ACP5):c.661G>A(p.Val221Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00645 in 1,611,542 control chromosomes in the GnomAD database, including 612 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V221V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.035 ( 313 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 299 hom. )

Consequence

ACP5
NM_001611.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.26

Variant links:

Genes affected

ACP5 (HGNC:124): (acid phosphatase 5, tartrate resistant) This gene encodes an iron containing glycoprotein which catalyzes the conversion of orthophosphoric monoester to alcohol and orthophosphate. It is the most basic of the acid phosphatases and is the only form not inhibited by L(+)-tartrate. [provided by RefSeq, Aug 2008]

ACP5 links:

LOC124904638 (HGNC:):

LOC124904638 links:

ZNF627 (HGNC:30570): (zinc finger protein 627) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF627 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002044946).

BP6

Variant 19-11576317-C-T is Benign according to our data. Variant chr19-11576317-C-T is described in ClinVar as [Benign]. Clinvar id is 464890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11576317-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACP5	NM_001611.5 linkuse as main transcript	c.661G>A	p.Val221Ile	missense_variant	4/5	ENST00000648477.1
LOC124904638	XR_007067140.1 linkuse as main transcript	n.105+964C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACP5	ENST00000648477.1 linkuse as main transcript	c.661G>A	p.Val221Ile	missense_variant	4/5		NM_001611.5	P3

Frequencies

GnomAD3 genomes

AF:

0.0354

AC:

5384

AN:

152100

Hom.:

312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00976

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.00931

AC:

2313

AN:

248382

Hom.:

132

AF XY:

0.00688

AC XY:

925

AN XY:

134522

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.00484

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00246

GnomAD4 exome

AF:

0.00343

AC:

5012

AN:

1459324

Hom.:

299

Cov.:

AF XY:

0.00289

AC XY:

2096

AN XY:

725980

show subpopulations

Gnomad4 AFR exome

AF:

0.127

Gnomad4 AMR exome

AF:

0.00575

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000405

Gnomad4 OTH exome

AF:

0.00691

GnomAD4 genome

AF:

0.0354

AC:

5389

AN:

152218

Hom.:

313

Cov.:

AF XY:

0.0349

AC XY:

2596

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.125

Gnomad4 AMR

AF:

0.00975

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.00642

Hom.:

Bravo

AF:

0.0407

ESP6500AA

AF:

0.128

AC:

566

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0119

AC:

1443

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

- -

Spondyloenchondrodysplasia with immune dysregulation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.27

T;T;T;T;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.50

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.88

.;.;.;.;D

MetaRNN

Benign

0.0020

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

L;L;L;L;L

MutationTaster

Benign

0.56

D;D;D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.44

.;N;N;.;N

REVEL

Benign

0.20

Sift

Benign

0.21

.;T;T;.;T

Sift4G

Benign

0.33

.;T;T;T;T

Polyphen

0.078

B;B;B;B;B

Vest4

0.095, 0.094

MPC

0.36

ClinPred

0.0037

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over